title: Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.
abstract: To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity.
authors.affiliation: US Army Medical Research Institute of Chemical Defense, Analytical Toxicology Division, Neurobehavioral Toxicology Branch, Aberdeen Proving Ground, MD 21010-5400, United States. Todd.Myers2@us.army.mil
authors.forename: Todd M
authors.initials: TM
authors.lastname: Myers
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Langston
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002794:Choline / Q000008:administration & dosage; D004032:Diet / Q000009:adverse effects*; D055423:Diet, Ketogenic; D019422:Dietary Sucrose / Q000633:toxicity; D004195:Disease Models, Animal; D005947:Glucose / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012999:Soman / Q000633:toxicity*; D013997:Time Factors
chemical_list: D002619:Chemical Warfare Agents; D019422:Dietary Sucrose; D012999:Soman; D005947:Glucose; D002794:Choline